Our goal is to obtain registration of a low antigenicity recombinant fVIII product for the treatment of patients with neutralizing antibodies against human fVIII. Such inhibitor patients include those with hemophilia A who develop alloantibodies when treated with replacement human fVIII, as well as patients with "acquired hemophilia" who develop autoantibodies against endogenous fVIII. Inhibitor patients have been successfully treated with plasma derived porcine fVIII (HYATE:C) in the US since 1986. HYATE:C is effective in such patients because antibodies against human fVIII frequently do not cross react with porcine fVIII. The cloning of full-length porcine fVIII has made possible the development of low antigenicity recombinant porcine fVIII and recombinant human/porcine fVIII constructs which merit clinical development. In Phase I of this grant applicant will obtain in vitro antigenicity data for HYATE:C, recombinant porcine fVIII and hybrid human/porcine fVIII. This data will be used as a basis for selecting a lead recombinant low antigenicity Nm protein that will then be tested for efficacy in vivo in a hemophilia mouse modeL Data will be collected in a manner so as enable its use in support of an Investigational New Drug (IND) filing for the candidate therapeutic construct with the United States FDA. PROPOSED COMMERCIAL APPLICATIONS: Approximately 26% of all hemophilia A patients develop antibodies. A significant portion cannot be successfully treated with human fVIII. A recombinant, low antigenicity fVIII product would compete well in the fVIII inhibitor patient market and be a first line therapy for "acquired hemophilia".